基于网络药理学分析海藻-昆布治疗乳腺癌的作用机制

Action mechanism of seaweed-kunbu in treatment of breast cancer based on network pharmacology

  • 摘要:
    目的 通过网络药理学方法分析海藻-昆布治疗乳腺癌的作用机制。
    方法 通过TCMSP数据库检索海藻-昆布的活性成分及其靶点。通过GeneCards和OMIM数据库获取乳腺癌的相关靶标, 并通过Cytoscape软件构建“药物-疾病靶点”网络图。利用String平台进行蛋白质-蛋白质相互作用(PPI)网络分析。采用R语言进行基因本体论(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析。采用分子对接技术验证关键化合物与靶点的结合能力,并通过体外实验进行功能验证。
    结果 本研究共获得海藻-昆布的有效化合物11个。海藻-昆布与乳腺癌高度相关的交集靶标为150个,筛选出丝氨酸/苏氨酸激酶1(AKT1)、p53肿瘤蛋白(TP53)、肿瘤坏死因子(TNF)、白细胞介素6(IL6)、血管内皮生长因子A(VEGFA)、JUN、胱天蛋白酶3(CASP3)、白细胞介素1B(IL1B)、MYC和人表皮生长因子受体(EGFR)共10个核心基因。GO分析表明,这些化合物可能参与信号转导、细胞凋亡、细胞增殖、炎症反应等生物过程。KEGG通路分析表明,主要富集信号通路为PI3K/Akt、MAPK和TNF等信号通路。分子对接和体外实验结果表明,海藻-昆布的主要化学成分岩藻甾醇对乳腺癌三阴型细胞BT-549具有抗增殖作用。
    结论 海藻-昆布可能通过多靶点、多通路来治疗乳腺癌,其主要化学成分岩藻甾醇可有效抑制BT-549细胞增殖活性。

     

    Abstract:
    Objective To analyze the mechanism of action of seaweed-kunbu in the treatment of breast cancer through network pharmacology.
    Methods The active ingredients and their targets of seaweed-kunbu were retrieved through the TCMSP database. Relevant targets for breast cancer were obtained through the GeneCards and OMIM databases, and "drug-disease target" network diagram was constructed using Cytoscape software. Protein-protein interaction (PPI) network analysis was performed using the String platform. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R language. Molecular docking technology was used to verify the binding ability of key compounds to targets, and functional verification was carried out through in vitro experiments.
    Results A total of 11 effective compounds were obtained from seaweed-kunbu in this study, among which 10 were related to breast cancer. There were 150 highly relevant intersecting targets between seaweed-kunbu and breast cancer, and 10 core genes including Serine/threonine kinase 1 (AKT1), p53 tumor protein (TP53), tumor necrosis factor (TNF), interleukin6 (IL6), vascular endothelial growth factor A (VEGFA), JUN, caspase 3 (CASP3), interleukin1B (IL1B), MYC and human epidermal growth factor receptor (EGFR) were screened out. GO analysis indicated that these compounds may be involved in biological processes such as signal transduction, apoptosis, cell proliferation, and inflammatory response. KEGG pathway analysis showed that the main enriched signaling pathways were PI3K/Akt, MAPK and TNF. Molecular docking and in vitro experimental results demonstrated that fucosterol, the main chemical component of seaweed-kunbu, had an antiproliferative effect on triple-negative breast cancer BT-549 cells.
    Conclusion Seaweed-kunbu may treat breast cancer through multiple targets and pathways, and its main chemical component fucosterol can effectively inhibit the proliferation activity of BT-549 cells.

     

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